Flt-4-positive vessel density correlates with vascular endothelial growth factor-d expression, nodal status, and prognosis in breast cancer.

PURPOSE: Metastasis to the regional lymph nodes through the lymphatic vessels is a common step in the progression of cancer and an important prognostic factor in many types of cancer. Recent evidence suggests that tumor lymphangiogenesis promotes lymphatic metastasis, and that the presence of Flt-4 on tumor blood and lymphatic vessels may play a important role in mediating lymphangiogenic factor-induced neovascularization. We assessed flt-4-positive vessel density (FVD) in breast cancer, and examined whether FVD associates with lymph node metastasis, VEGF-D expression, or prognosis. EXPERIMENTAL DESIGN: One hundred three invasive breast carcinomas with long-term follow-up were included in our study. Flt-4 was assessed using immunohistochemistry, then we analyzed the relationship between FVD and lymph node status, as well as VEGF-D expression and other established clinicopathological parameters. The relationship between FVD and prognosis was also investigated. RESULTS: Mean FVD of "hot spot" was 29.3 +/- 22.5 for each case. FVD was correlated significantly with lymph node metastasis (P < 0.0001), VEGF-D expression (P = 0.0019), tumor size (P = 0.0015), estrogen receptor (P = 0.0211), progesterone receptor (P = 0.0462), and c-erbB-2 (P = 0.0326). Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that high FVD was associated with both worse disease-free survival (P = 0.0035) and overall survival (P = 0.0336). CONCLUSIONS: Increased FVD was correlated with lymph node metastasis and VEGF-D expression. High FVD may be a significant unfavorable prognostic factor for long-term survival in breast cancer. It is possible that Flt-4 becomes a target for antiangiogenic therapy to breast cancer.     

Cost-benefit analysis methods for assessing air pollution control programs in urban environments—A review

The most common method of evaluating beneficial impacts of environmental policies is cost-benefit analysis (CBA). In the present review, CBA methods for air pollution impacts are reviewed. Three types of air pollution effects are identified, including health, productivity, and amenity. Market valuation, stated preference methods, and revealed preference methods are identified for valuing benefits. Three types of costs are deseribed, including private sector costs, societal costs, and governmental regulatory costs. A benefits valuation approach based on Freeman's principals is described. A costs valuation approach based on U.S. Environmental Protection Agency and Dixon et al. principals is deseribed. Limitations associated with estimates of benefits and costs are summarized. Input assumptions and results are compared for several existing air pollution control analyses. The importance of CBA in environmental policy studies is discussed. Our conceptual approaches should be useful in analyses of urban air pollution impacts and air pollution prevention policies.     

Correlation between nuclear grade and biological prognostic variables in invasive Breast Cancer

BACKGROUND: Grading of carcinomas is an estimation of differentiation. Nuclear grading is the cytological evaluation of tumor nuclei in comparison with the nuclei of normal mammary epithelial cells. Because nuclear grading does not involve an assessment of the growth pattern of the tumor, it applies not only to invasive ductal carcinoma but also to other subtypes of breast carcinoma. METHODS: A total of 215 primary breast carcinomas obtained from the Affiliated Kihoku Hospital of Wakayama Medical College were enrolled in our present study. Nuclear grade was evaluated according to the criteria of the National Surgical Adjuvant Study of Breast Cancer (NSAS-B) protocol. Immunohistochemistry was also performed to determine Bcl-2, p53, c-erbB-2, estrogen receptor (ER) and MIB-1 expression in paraffin-embedded tissues for all cases. RESULTS: Thirty-two (14.9%) of the patients were graded as 1,124 (57.7%) as 2, and 59 (27.4%) as 3. Nuclear grade displayed a negative correlation with Bcl-2 expression (r=-0.308, p<0.0001), and a positive correlation with c-erbB-2 overexpression (r= 0.172, p=0.0117) and tumor proliferative index labeling by MIB-1 (r=0.485, p<0.0001). CONCLUSIONS: These results imply that nuclear grade is related to the characteristics of tumor biology, indicating that the morphology and biology of breast cancer are tightly linked. Our present results also suggest that adding the nuclear grade to the pathological diagnosis of invasive breast carcinoma may be clinically useful for predicting tumor behavior, for example aggressiveness, and for prognostication.     

Fetal growth promotion in allergic children

Several in vitro studies have suggested the presence of Th2-skewed immunity during pregnancy in infants with atopic diseases. Our study indicated that allergic infants showed a higher birth weight and shorter gestational period at birth than those of non-allergic peers. Moreover, allergic mothers gave birth to neonates whose birth weights and gestational ages were higher and shorter than those of the non-allergic mothers, respectively. Thus, our data clearly demonstrated the promotion of intrauterine growth, either in the allergic children, or allergic mothers. Such an intrauterine environment favorable for the fetal growth may also accelerate the development of allergic diseases in their offspring that are most probably caused by the Th2-oriented immunity.     

Phosphonate O-deethylation of [4-(4-bromo-2-cyano-phenylcarbamoyl) benzyl]-phosphonic acid diethyl ester, a lipoprotein lipase-promoting agent, catalyzed by cytochrome P450 2C8 and 3A4 in human liver microsomes.

NO-1886 ([4-(4-bromo-2-cyano-phenylcarbamoyl) benzyl]-phosphonic acid diethyl ester) increases lipoprotein lipase activity, resulting in a reduction in plasma triglycerides and an increase in high-density lipoprotein cholesterol. The metabolism of NO-1886 in human liver was investigated in the present study. Ester cleavage of NO-1886 from diethyl phosphonate to monoethyl phosphonate was the major metabolic pathway catalyzed by cytochrome P450. In addition, the minor metabolic pathway in human liver was the hydrolysis of the amide bond of NO-1886 by a specific cytosolic esterase. Eadie-Hofstee plots of phosphonate O-deethylation of NO-1886 in human liver microsomes showed a biphasic curve, indicating low- and high-K(m) components. Inhibition experiments with chemical inhibitors and antibodies against various cytochrome P450 isoforms suggested the involvement of CYP2C8 and CYP3A in the phosphonate O-deethylation. Recombinant CYP3A4 and CYP2C8 expressed in baculovirus-infected insect cells and human lymphoblastoid cells exhibited a high activity for phosphonate O-deethylation of NO-1886. The recombinant cytochrome P450 enzymes indicated that CYP2C8 and CYP3A4 were responsible for the low- and high-K(m) components in human liver microsomes, respectively. The selectivity of CYP2C8 in catalyzing phosphonate O-deethylation indicates that coadministration of drugs that are metabolized by the same enzyme requires careful consideration.     

Newborn extracorporeal lung assist using a novel double lumen catheter and a heparin-bonded membrane lung

We report the clinical application of a novel double lumen catheter for veno-venous extracorporeal lung assist (ECLA) and the use of a heparin-bonded hollow fiber membrane lung, in the treatment of newborn respiratory failure. The outer lumen of the double lumen catheter was 14 Fr and was used for blood drainage; while the inner 8 Fr catheter was used for blood return. The double lumen catheter was made of spiral wire reinforced polyurethane, with a wall thickness of 0.25 mm. The hollow fiber membrane was made of non-microporous polyolefin, and was not permeable to water or plasma. We used this system to treat a newborn patient with meconium aspiration syndrome. Heparin was infused continuously at a rate of 18–25 units/kg/h, equal to 1/3 of the usual amount when a non-heparin bonded ECLA system was used and maintaining the activated clotting time near 120 s. Bleeding from cutdown sites was negligible. Only the right internal jugular vein was sacrificed. The patient was successfully weaned from ECLA and appears normal one year following discharge.     

Epidural hematoma after epidural anesthesia: a case report of non-surgical management

Neuraxial block with intraoperative intravenous (IV) heparin use is considered to be a safe technique. The risk of epidural hematoma is low as long as concomitant anti-coagulation is not used [ASRA: Neuraxial Anesthesia and Anticoagulation Consensus Statements, 1998]. We describe a patient who developed epidural hematoma under those circumstances and was successfully treated without surgical intervention.

A 75-year-old female underwent aorto-mesenteric arterial bypass for chronic mesenteric ischemia. Combined general and epidural anesthesia was used and IV heparin (total 6000 IU) was given intraoperatively. In the recovery room, aspiration of blood was noted through the epidural catheter. The next day, she developed severe back pain without sensory or motor deficit. Magnetic resonance imaging (MRI) scan revealed an epidural hematoma with spinal cord compression. Neurosurgical consultation resulted in a decision to monitor for neurological changes. She never developed a neurological deficit and was discharged from the hospital on post-operative day 7.

Our case suggests that epidural hematoma may not be uncommon phenomena in patients with neuraxial block and intraoperative IV heparin use. Implications for the decision as to which of these patients should be imaged and which should not are discussed.